Correspondence *Department of Urology, David Geffen School of Medicine, University of California–Los Angeles, Box 951738, 66-124 CHS, 10833 LeConte Avenue, Los Angeles, CA 90095, USA

Email jgore@mednet.ucla.edu

The case

A 66-year-old white male with a medical history of hypertension, hyperlipidemia, and benign prostatic hyperplasia presented for evaluation of an elevated PSA level of 6.2 ng/ml, detected during routine prostate cancer screening. He reported a 5-year history of obstructive urinary symptoms, for which he was taking tamsulosin 0.4 mg nightly; his American Urological Association symptom index score confirmed moderate symptoms, with a total score of 17 of 35 possible points. He reported erections that were diminished, but adequate for intercourse. He had no bowel complaints. He had no surgical history and no family history of prostate cancer; he was married, and he had never smoked.

On examination, the patient had a healthy appearance, with a normal body habitus. His abdomen was soft. His external genitalia seemed normal. Digital rectal examination revealed a slightly enlarged, smooth prostate, with no palpable nodules.

He subsequently underwent a transrectal ultrasound and ultrasound-guided prostate needle biopsy. Ultrasound revealed a 39-ml gland with no hypoechoic lesions or calcifications. Following a periprostatic nerve block, a systematic 12-core prostate needle biopsy was performed. Adenocarcinoma of the prostate of Gleason sum 7 (3 + 4) was detected in three of six cores from the right lobe; 20% of the affected cores contained cancer. The patient subsequently returned for a discussion of his diagnosis and management options.

Following a full discussion of the risks and benefits of the available treatment options, the patient opted for radical prostatectomy. He underwent an uncomplicated bilateral cavernosal nerve-sparing retropubic radical prostatectomy. His postoperative course was uneventful. Pathological analysis revealed a pathologic stage T2c organ-confined adenocarcinoma of Gleason sum 7 (3 + 4), involving both lobes of the prostate. Surgical margins were negative. Every 3 months, he underwent physical examination and his history and serum PSA levels were evaluated. At 12 months postoperatively, he was continent, with no obstructive or irritative voiding symptoms. With the use of a phosphodiesterase-type-5 inhibitor, he achieved erections adequate for intercourse. His PSA level remained undetectable.

Discussion of diagnosis

On the basis of the physical examination, PSA level, and biopsy results, the patient was diagnosed with clinical stage T1c prostate cancer. From Partin tables, we know he has a 63% chance of organ-confined disease and a 2% chance of lymphatic spread. He is at intermediate risk for biochemical recurrence following treatment, according to the D'Amico stratification. From life tables generated by the Centers for Disease Control, he has a life expectancy of 16.6 years.¹

Treatment and management

Any discussion of treatment begins with the possibility that newly diagnosed prostate cancers are clinically indolent and might not require immediate therapy. A competing-risk analysis of men with clinically localized prostate cancer treated with observation in the early 1980s has shown that men with low-grade disease, defined as Gleason sum 2–4, are unlikely to die of prostate cancer within 20 years.² For a 66-year-old man with Gleason sum 7 histology, the 15-year prostate-cancer-specific mortality rate without treatment is approximately 50%. Results from a randomized Scandinavian trial comparing radical prostatectomy with watchful waiting indicated an increased risk of death from prostate cancer in men allocated to the watchful-waiting group.³ Beyond the potential impact on survival, conservative management of prostate cancer could confer health-related quality-of-life (HRQOL) detriments. Surprisingly, many more men on observation protocols for clinically localized prostate cancer develop functional impairments over time, compared with similarly aged men without prostate cancer.⁴ Men allocated to watchful waiting in the Scandinavian trial were 40% more likely to report obstructive urinary symptoms at interval follow-up than were men treated with radical prostatectomy.⁵ On the basis of these data, we encouraged the patient to pursue active treatment.

We always discuss with our patients the techniques and recovery involved with the three most common primary treatments for clinically localized prostate cancer: radical prostatectomy; external-beam radiation therapy (EBRT); and brachytherapy. We discuss our treatment goals—prioritizing cancer control, maintenance of urinary continence and sexual function, and avoidance of bowel complications. No randomized, controlled trial has proven the superiority of one treatment modality in terms of cancer control, so discussion of treatment options often focuses on HRQOL outcomes associated with individual treatments.

Any discussion of HRQOL outcomes of the various treatments for clinically localized prostate cancer is inherently biased. Unlike the nomograms and tables that have been published for the prediction of surgical and survival outcomes, no standard tables, figures, or nomograms are available to aid physicians in counseling patients with regard to treatment-related effects on HRQOL. Lacking an individualized approach to patient concerns regarding HRQOL, we must turn to the literature to support our patient discussions. A PubMed search for "quality of life" and "prostate cancer" yields 1,745 results. Most investigations employ cross-sectional analyses or retrospective data collection; few studies examine longitudinal HRQOL prospectively. Furthermore, surgeon variability, known to affect morbidity and mortality outcomes following radical prostatectomy,⁶ probably has similar effects on postoperative HRQOL. A 'treatment center effect' could likewise impact on EBRT and brachytherapy outcomes. Published continence and potency rates by a high-volume prostate surgeon or radiation oncologist might not be generalizable to the average practitioner. Thus, specialists caring for prostate cancer patients must apprise themselves of their individual outcomes. To that end, it becomes mandatory to assess our results with patient-derived instruments, to eliminate our own bias and desire for positive outcomes.

We generally begin discussions of post-treatment HRQOL with a review of the domains typically measured in prostate cancer patients. Other than a brief impairment in physical functioning among radical prostatectomy patients, general HRQOL is not appreciably affected by treatment for localized prostate cancer. The overwhelming majority of radical prostatectomy patients return to baseline physical functioning within 2 months of surgery. Beyond general HRQOL, validated instruments are available that assess prostate-cancer-specific HRQOL. The two most commonly used tools are the UCLA Prostate Cancer Index and the Expanded Prostate Cancer Index Composite, which both focus on three disease-specific HRQOL domains: urinary control; sexual function; and bowel function. The American Urological Association symptom index, with a brief assessment of obstructive and irritative urinary symptoms, combines with the Prostate Cancer Index or Expanded Prostate Cancer Index Composite to comprehensively measure the dysfunctions that most commonly confront patients treated for localized prostate cancer.

With respect to urinary symptomatology, radiation therapy is more likely to exacerbate obstructive and irritative voiding symptoms and have a minimal effect on urinary control.^{7, 8} Following brachytherapy, approximately a third of patients experience urinary retention within 1 week of treatment, with a subsequent relapse of obstructive symptoms at 24 months.⁹ High rates of incontinence in men undergoing postbrachytherapy transurethral resection of the prostate limit surgical management of severe symptoms in these men.¹⁰ Radical prostatectomy carries a substantial risk of postoperative urinary incontinence, but has a beneficial effect on obstructive urinary symptoms, and no effect on irritative voiding symptoms.¹¹ We typically quote patients a 10% rate of mild stress urinary incontinence at 1 year following radical prostatectomy. Most investigations confirm low rates of urinary incontinence when a more anatomic approach to the apical dissection of the prostate and preservation of the bladder neck are used. Dissemination of these techniques could explain the low rates of urinary incontinence in community-based analyses, including 2-year outcomes reported in the Prostate Cancer Outcomes Study (PCOS) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).^{12, 13, 14} EBRT carries an increased rate of irritative and obstructive symptoms and a decreased rate of incontinence compared with radical prostatectomy.

Sexual-function outcomes reported in the literature are more disparate. Many investigators focus on a patient's ability to have penetrative intercourse as the hallmark of successful return of sexual function. We prefer to consider sexual function as a more holistic outcome, rather than relegating it to a simple yes/no checkbox. In our experience, despite patient reports of potency before treatment, surprisingly few have 'normal' sexual function when assessed by baseline patient-directed questionnaires. Thus, we typically outline a goal of returning to baseline sexual function following treatment rather than regaining potency per se. Younger patients, those with better sexual function scores before treatment, and those who undergo bilateral nerve-sparing surgery are more likely to recover baseline sexual function. Patients undergoing radiation therapy experience less initial impairment, but sexual function scores tend to decline progressively over the subsequent 5 years.¹⁵ We inform patients with good baseline sexual function that, following bilateral nerve-sparing surgery, a third will recover baseline sexual function within 2 years and two-thirds will achieve adequate sexual function with or without the use of erectile aids, and that sexual function scores improve with time.

From PCOS and CaPSURE data we can extrapolate expected outcomes for the general practitioner. Although baseline scores were collected retrospectively, follow-up scores demonstrate expected recovery trends for the community urologist or radiation oncologist. Patients enrolled in the PCOS who underwent EBRT or radical prostatectomy had similar baseline urinary control and potency;¹² at 2 years follow-up, 96% of EBRT patients and 78% of radical-prostatectomy patients were considered continent. Before treatment, 65% of EBRT patients and 61% of radical-prostatectomy patients were 'potent'; at 2 years post-treatment, 45% and 20% of patients, respectively, reported erections firm enough for intercourse. Results from CaPSURE demonstrate initial postoperative declines in urinary-control scores among radical-prostatectomy patients that return to adjusted means on par with those of EBRT recipients 1 year after treatment.¹⁴ Conversely, sexual function scores reflect poor outcomes for both treatment modalities.¹³ Although initially better, sexual function scores among EBRT patients decline with time, such that scores are comparable between radical prostatectomy and EBRT patients 24 months after treatment. Mean sexual function scores of 28 and 30 of a 100 possible points among radical prostatectomy and EBRT patients, respectively, fall well below cutoff values consistent with potency.

Bowel symptomatology is often overlooked in urologists' discussions of HRQOL. Although more commonly associated with radiation therapy, bowel dysfunction affects those treated with any of the three modalities. Gastrointestinal symptoms completely resolve within 1–2 months of surgery (usually a constipating effect of postoperative narcotics), but can persist following EBRT or brachytherapy. Distress related to bowel dysfunction can be debilitating, although newer EBRT protocols minimize radiation dose to tissues surrounding the prostate, such as the rectum. Several comparative studies examining patients treated for clinically localized prostate cancer have demonstrated that bowel dysfunction, specifically fecal leakage and defecation urgency, might have a greater effect on general HRQOL than do other disease-specific dysfunctions. Severe bowel distress affects 15–20% of EBRT and brachytherapy recipients 24 months post-treatment; bother related to bowel dysfunction after radical prostatectomy is uncommon. The need for diverting colostomy following EBRT is rare.

After reviewing these data, the patient decided that surgery would best address both the cancer and his moderate obstructive urinary symptoms. He experienced daily distress from his lower urinary tract symptoms and chose to avoid treatment options that might exacerbate those symptoms.

Conclusion

Discussion of the adverse effects of treatment for localized prostate cancer requires a thorough knowledge of the differential HRQOL outcomes associated with the three main treatment options. Radical prostatectomy has a greater initial impact on urinary control and sexual function than either radiation modality has, but both domains demonstrate progressive improvement with time. Bowel dysfunction commonly affects patients undergoing EBRT and brachytherapy, but has a minimal impact on radical prostatectomy recipients. Although urinary control and sexual function are less affected by radiation therapy immediately following treatment, a progressive decline with time has been demonstrated. Brachytherapy can exacerbate obstructive and irritative urinary symptoms. From the physician's perspective, proper counseling mandates knowledge of one's own patients' outcomes rather than abstraction of results from the literature.

References

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Subject areas under which this article appears: Prostate cancer